DEEP LEARNING IN PAIN MMT

A. General

Background Concepts = Nociceptor depol → AP → SC dorsal horn → spinothalamic tracts → thalamus → cortex; mod: ion channels, NTs, GPCRs.

Assessment of Pain = QN/QL metrics; VAS, fMRI BOLD, qEEG; biomarkers (IL-6↑, TNF-α↑); psychometrics → multidimensional pain matrix.

Tx of Pain: Pharmacotherapy = Opioids (μ-R agon), NSAIDs (COX-inh), cannabinoids (CB1/CB2), Na⁺-blockers, NMDA-antag; polypharm → receptor crosstalk.

Tx of Pain: Procedural = LESI, RFA, SCS; local depol block → ↓AP freq; neuroablation vs neuromod.

Tx: Psychological, Physical, Integrative = CBT (cog reframe), PT (mechanotransduction), yoga/meditation (HRV↑, cortisol↓); placebo → endogenous opioid/DA pathways.

B. Clinical States

Taxonomy: Classification of Pain Syndromes = Acute vs chronic; nociceptive vs neuropathic vs nociplastic; ICD-11 IASP schema.

Chronic Widespread Pain Syndromes = Fibromyalgia; ↑CNS wind-up, ↓5-HT/NE; HPA dysreg; mitochondrial bioenergetics↓.

Acute Pain, Trauma, Postop = Tissue injury → PGE2↑, bradykinin↑; nociceptor sensitization; central plasticity → hyperalgesia.

Musculoskeletal Pain = Myofascial trigger pts; cytokine↑, lactate↑; mechano-nociceptor → integrin-FAK signaling.

Cancer Pain and Cancer-related Pain = Tumor invasion → peri-neural inflammation; NGF↑, VEGF↑; bone mets → osteoclast RANKL↑.

Visceral Pain = Organ stretch → TRPV1/ASIC activation; vagal/C-fiber afferents; central viscerotopy.

Headache and Orofacial Pain = Migraine: CGRP↑, cortical spreading depol; trigeminal V ganglion sensitization.

Neuropathic Pain = Nerve lesion → ectopic firing; NaV1.7 mut, microglia BDNF↑, disinhibition (GABA↓).

Special Cases = Phantom limb (cortical remap), CRPS (symp-sensitization, cytokine storm), pediatric pain (neuro-dev immaturity).

A. General

1. Background Concepts

a. Anatomy, Physiology, and Pharmacology of Nociception

i. Anatomy and Physiology of Nociception

The somatosensory system involves specialized nociceptors that detect noxious stimuli. A-delta fibers, which are myelinated, transmit fast, sharp pain signals, while C fibers, unmyelinated, convey slow, dull, or aching pain. The autonomic nervous system modulates pain through sympathetic effects like vasomotor and sudomotor changes in chronic states, and parasympathetic influences on gastrointestinal or visceral pain. Somatic and visceral peripheral nerves feature free nerve endings as nociceptors, which are polymodal and respond to mechanical, thermal, or chemical stimuli. At the spinal level, signals enter the dorsal horn, organized into laminae I-VI, with lamina II (substantia gelatinosa) playing a key role in gating. In the brain, pathways involve the midbrain (periaqueductal gray for descending modulation), thalamic nuclei for sensory relay, cerebral cortex (anterior cingulate and somatosensory areas) for perception, and limbic system (amygdala) for emotional processing.

ii. Mechanisms of Nociceptive Transmission and Modulation

Nociceptive transmission begins peripherally with transduction at nociceptors, involving ion channels like transient receptor potential vanilloid 1 (TRPV1) for heat and capsaicin, or acid-sensing ion channels (ASICs) for pH changes. Signals propagate via action potentials along afferent fibers, releasing neurotransmitters such as glutamate and substance P in the dorsal horn, exciting postsynaptic neurons. Modulation occurs through peripheral mechanisms like afferent fiber sensitization by inflammatory mediators (prostaglandins, cytokines like interleukin-1 and tumor necrosis factor-alpha), leading to lowered thresholds. Centrally, spinal transmission in the dorsal horn involves wide dynamic range neurons that integrate inputs, with spinal processing enabling wind-up (temporal summation via N-methyl-D-aspartate receptor activation) and reflexes like withdrawal. Medullary dorsal horn handles trigeminal pain. Brain-level changes in chronic pain include cortical reorganization, such as expanded somatotopic maps seen on functional magnetic resonance imaging. Acute pain involves direct tissue damage pathways, inflammatory pain amplifies via immune cell recruitment, and neuropathic pain arises from ectopic firing post-nerve injury. Somatic pain is localized due to precise innervation, while visceral pain is diffuse and referred due to convergence. Referred pain results from viscero-somatic convergence in the dorsal horn, e.g., cardiac ischemia referring to the arm.

iii. Peripheral and Central Sensitization

Peripheral sensitization involves lowered nociceptor thresholds due to inflammatory soup (bradykinin, prostaglandins, nerve growth factor), activating intracellular kinases like protein kinase A and C, which phosphorylate ion channels (e.g., TRPV1 sensitization). This leads to hyperalgesia and allodynia, with implications for treatment like targeting cyclooxygenase for prostaglandin reduction. Central sensitization manifests as synaptic plasticity in the dorsal horn, with long-term potentiation via N-methyl-D-aspartate receptors allowing calcium influx, activating pathways like mitogen-activated protein kinase for gene expression changes. Neuroimmune signaling involves microglia releasing brain-derived neurotrophic factor, shifting inhibition to excitation. Psychosocial factors like stress facilitate central sensitization by downregulating descending inhibition via altered serotonin and norepinephrine pathways. Descending modulation includes inhibition from periaqueductal gray-rostral ventromedial medulla-spinal circuits (opioid, serotonergic) and facilitation from ON cells. Neurotransmitters such as gamma-aminobutyric acid and glycine provide inhibition, glutamate and substance P excitation, and opioids presynaptic inhibition. Pharmacological modulation in the brain targets mu-opioid receptors in periaqueductal gray or serotonin-norepinephrine reuptake for enhanced descending control. Other aspects include voltage-gated sodium channels (Nav1.7) in genetic pain disorders.

b. Development of Pain Systems

i. Anatomical development begins with nociceptors forming by week 7 of gestation, thalamocortical connections by week 24, and a fully functional system by birth.

ii. Pain behavior in the fetus includes withdrawal reflexes from week 19; in newborns, it manifests as crying and facial expressions assessed by scales like the Neonatal Facial Coding System.

iii. Physiologic and behavioral assessment measures in infants, such as the Face, Legs, Activity, Cry, Consolability scale, are valid but limited by subjectivity and inability to capture emotional components.

iv. Long-term consequences of neonatal pain include heightened sensitivity in adulthood due to epigenetic changes altering the hypothalamic-pituitary-adrenal axis.

v. Pediatric traumatic experiences, like abuse, contribute to central sensitization and increased chronic pain risk via posttraumatic stress disorder amplifying pain pathways.

vi. Other developmental aspects include prematurity altering pain thresholds and genetic factors like catechol-O-methyltransferase gene influencing maturation.

c. Research Methodology of Pain

i. Epidemiology: Use data to measure burden (prevalence, incidence); e.g., chronic pain prevalence 20-30%. Risk factors guide treatment, such as smoking increasing back pain risk.

ii. Principles of clinical trial design: Inclusion/exclusion based on history, exam, lab; hypothesis development as null/alternative.

iii. Research study design: Observational for association strength (odds ratio/relative risk), limitations include bias; cohort for natural history/predictors (e.g., 10-20% acute to chronic transition); correlational/case reports/retrospective/cross-sectional for hypothesis generation; controlled trials as randomized, prospective, experimental for causality.

iv. Data analysis: Types (parametric/continuous/ratio/categorical/dichotomous); distributions (normal for t-test; non-normal for Mann-Whitney); descriptive statistics (confidence intervals/means/proportions); probability testing/sampling.

v. Statistical analysis: Power calculations (beta=0.2); effect size (Cohen's d); significance/power/type I/II errors related to sample size.

vi. Evaluating study results: Minimal clinically important difference (e.g., visual analog scale change of 2); regression (dependent/explanatory/confounding variables); correlation coefficients; tests (t-test/analysis of variance/linear regression/chi-squared/odds ratios/logistic regression/effect size/power/number needed to treat/number needed to harm).

vii. Understanding basic research concepts: Reliability/validity; sensitivity/specificity; randomization to minimize bias; use of controls.

viii. Methods of assessing scientific evidence: Grades (I-IV); Cochrane systematic reviews; bias/chance/confounding reduced by blinding/randomization; publication bias via funnel plots.

ix. Ethical standards: Principles of justice/autonomy/beneficence/nonmaleficence; professionalism/quality assurance; design (scientific validity/fair selection/favorable risk-benefit/respect for subjects/institutional review board); informed consent; conflicts of interest/disclosure.

x. Other: Qualitative research for patient perspectives.

d. Teamwork and Care Coordination

i. Coordination of care with colleagues and health systems is crucial for patient outcomes, e.g., multidisciplinary teams reducing hospitalizations in chronic pain.

ii. Mentorship and personal well-being: Balance professional demands with personal life to prevent burnout.

iii. Participation in quality assurance: Identify system errors via root cause analysis.

iv. Optimizing communication, transitions, and hand-off procedures: Use Situation-Background-Assessment-Recommendation to minimize errors.

v. Other: Telemedicine for coordination.

e. Legal and Regulatory Issues

i. Elements of medical malpractice: Duty, breach, causation, damages.

ii. Legal actions and consequences: National Practitioner Data Bank, Closed Claims findings, professional liability insurance.

iii. Laws related to controlled substances, including opioids and cannabinoids: Drug Enforcement Administration scheduling, Prescription Drug Monitoring Program checks.

iv. Patient privacy: Principles of confidentiality, access to records, protected health information.

v. Health Insurance Portability and Accountability Act compliance.

vi. Workers’ compensation and disability evaluations.

vii. Reporting impaired healthcare professionals: Mandatory ethical obligations.

viii. Other: Telemedicine regulations.

2. Assessment of Pain

a. Clinical Pain Evaluation

i. Pain as a subjective, multidimensional experience follows the biopsychosocial model; International Association for the Study of Pain definition as an unpleasant sensory and emotional experience associated with actual or potential tissue damage; distinction between nociception (neural process) and pain (perception); acute pain is protective, chronic is maladaptive.

ii. Terminology: Analgesia (absence of pain), hyperalgesia (increased pain from noxious stimuli), hypoalgesia (decreased), anesthesia (no sensation), hyperesthesia (increased sensation), hypoesthesia (decreased), paresthesia (abnormal sensation without stimulus), dysesthesia (unpleasant abnormal). Spontaneous versus evoked pain; hyperpathia (explosive pain), allodynia (pain from non-noxious stimuli), anesthesia dolorosa (pain in anesthetic area); radicular pain (dermatomal distribution), radiculopathy (nerve root dysfunction).

iii. Measurement: Subjective challenges and limitations; population measures for epidemiology; direct via self-report (visual analog scale/numeric rating scale); indirect via behavioral observations.

iv. Pain sensory testing: Sensory threshold (detection), pain threshold (onset), tolerance (maximum endurance); mechanical allodynia types (punctate/dynamic/static); cold/warm allodynia; quantitative sensory testing defines methods and mechanisms, e.g., thermal/mechanical thresholds.

v. Components: Basic medical examination including history, physical, mental status; body functions/structures/motor/sensory/autonomic assessment; biomedical including treatment response, pharmacological management, nutritional/sleep/sexual/general health status.

vi. Other: Multidimensional tools like McGill Pain Questionnaire.

b. Placebo and Pain

i. Placebo definition and incidence: Non-specific treatment effect, occurring in 30-40% of pain trials.

ii. Historic aspects: Rooted in conditioning responses.

iii. Mechanisms and interpretation: Expectancy activates endogenous opioids (reversible by naloxone) and dopamine in reward circuits (nucleus accumbens); classical conditioning pairs cues with relief; interpretation as real neurobiological response involving prefrontal cortex modulation of pain pathways.

iv. Role in clinical trials: Controls for bias in double-blind designs.

v. Response bias: Influenced by patient reporting.

vi. Ethics: Limited in practice if effective treatments exist; acceptable in trials with equipoise.

vii. Regression to the mean: Natural symptom fluctuation misattributed to intervention.

viii. Placebo as treatment modality: Harness expectancy ethically.

ix. Nocebo effect: Negative expectations amplify pain via cholecystokinin release and anxiety circuits, leading to hyperalgesia.

x. Other: Contextual effects in clinical encounters.

c. Assessment of Functional Outcomes and Disability

i. Functioning and disability: Body functions/structures impairments (sleep/attention/emotional/cognitive); activities/participation limitations (exercise tolerance/sexual function/mobility); developing rehabilitation programs assessing static/dynamic flexibility, strength, coordination, agility for joint/spinal/soft tissue conditions; validated tools like Short Form-36 or Roland-Morris Disability Questionnaire.

ii. Contextual factors: Environmental (health services/workplace policies/professional attitudes); personal (family/workplace/cultural/religious/recreational/leisure activities).

d. Assessment of Psychosocial and Cultural Aspects of Pain

i. Pain as biopsychosocial: Validated tools for older adults/cognitively impaired/behavioral/diverse backgrounds; influences from social/cultural/psychological/physical/genetic/age/health literacy/religion/family; multimodal (single practitioner)/multidisciplinary (team)/referrals; assess nutritional/sleep/sexual/general health/past treatments/pharmacological; special populations (pregnant/older/mental health disorders/substance use/opioid-tolerant).

ii. Psychological assessment: Home/family/employment/financial/recreational/cultural beliefs; impact of physical/emotional/sexual abuse history; psychological history/stresses/coping; beliefs about pain/prognosis/life interference/lifestyle/identity changes; screening questionnaires like Patient Health Questionnaire-9 or Generalized Anxiety Disorder-7.

e. Sex and Gender Issues in Pain

i. Definitions: Sex (biological), gender (social constructs).

ii. Sex differences in epidemiology: Females higher chronic pain prevalence (migraine/fibromyalgia), modulated by age/reproductive history (e.g., menopause increases musculoskeletal pain).

iii. Nociceptive responses and perception: Females show greater sensitivity, influenced by hormones (estrogen amplifies in animal models).

iv. Analgesic response: Sex differences (females more adverse effects from opioids); intra-sex variations (menstrual cycle phases).

v. Biologic and psychosocial contributions: Genetic/hormonal factors plus catastrophizing.

vi. Treatment seeking/delivery/effectiveness: Gender biases may lead to undertreatment in females.

vii. Other: Transgender hormone therapy influences.

f. Imaging and Electrodiagnostic Evaluation

i. Magnetic resonance imaging/functional magnetic resonance imaging/magnetic resonance spectroscopy: Uses for structure/function/metabolism; limitations include overuse/false positives.

ii. Electromyography/nerve conduction velocity/evoked potentials: Assess nerve/muscle function; limitations operator-dependent.

iii. Quantitative sensory testing: Mechanisms via thresholds; limitations subjective.

iv. Skin punch biopsy: Innervation density for small fiber neuropathy.

v. Laser-evoked potentials: A-delta/C fiber assessment; limitations expensive.

vi. Positron emission tomography: Metabolic activity in chronic pain brain changes.

vii. Nuclear medicine bone scan: Metabolic activity; limitations non-specific.

viii. Electroencephalography: Cortical responses to evoked potentials.

ix. Other: Computed tomography for bone detail.

3. Treatment of Pain: Pharmacotherapy

a. Opioids

i. Mechanism of action: Bind mu/kappa/delta G-protein-coupled receptors, inhibiting adenylyl cyclase, opening potassium channels (hyperpolarization), closing calcium channels; reduces nociceptive transmission presynaptically (decreased glutamate release) and postsynaptically in dorsal horn/brain. Kappa receptors may contribute to dysphoria and diuresis, delta to analgesia and mood effects.

ii. Pharmacokinetics, pharmacodynamics, pharmacogenomics: Dose equivalence (e.g., morphine 10 mg oral = hydromorphone 1.5 mg); absorption varies by route, distribution lipid-soluble, metabolism via cytochrome P450 (e.g., CYP2D6 for codeine), excretion renal/hepatic (dose adjust in impairment); pharmacogenomics like CYP2D6 variants affect conversion (poor metabolizers get less effect from codeine).

iii. Drug interactions/indications/contraindications: Central nervous system depressants increase respiratory depression; indicated for acute/chronic non-cancer/cancer pain. Interactions include monoamine oxidase inhibitors (serotonin syndrome with tramadol/tapentadol) and cytochrome P450 inducers/inhibitors altering metabolism.

iv. Specific drugs: Buprenorphine (partial agonist/antagonist at mu, antagonist at kappa); methadone (long-acting mu agonist with N-methyl-D-aspartate antagonism, reducing hyperalgesia); codeine (prodrug to morphine); fentanyl (high potency, rapid onset); hydromorphone; morphine; oxycodone; oxymorphone; tapentadol (mu agonism plus norepinephrine reuptake inhibition for neuropathic component); tramadol (weak mu agonism plus serotonin-norepinephrine reuptake inhibition).

v. Routes: Oral/sublingual/buccal/rectal/transdermal/topical/subcutaneous/intramuscular/intravenous/intra-articular/epidural/spinal.

vi. Compare use in acute/chronic non-cancer/cancer: Acute short-term; chronic non-cancer controversial (limited evidence); cancer palliative.

vii. Effectiveness: Evidence-based short-term; tolerance leads to dose escalation; long-term may decrease function.

viii. In chronic non-cancer: Use in substance use disorders; addiction versus pharmacological tolerance/withdrawal.

ix. Rationale for rotation/discontinuation: Cross-tolerance requires equivalence calculation; taper slowly to avoid withdrawal.

x. Adverse effects: Opioid-induced hyperalgesia (paradoxical pain via N-methyl-D-aspartate activation); tolerance; immune/endocrine/cardiovascular/tumor growth/cognitive effects; impact on driving.

xi. Other: Naloxone reversal.

b. Antipyretic Analgesics: Nonsteroidals, Acetaminophen, and Phenazone Derivatives

i. Mechanism: Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase-1/2, reducing prostaglandins (peripheral anti-inflammatory and central analgesia); acetaminophen central cyclooxygenase/peroxidase inhibition, possibly involving cannabinoid receptors and descending serotonergic pathways.

ii. Pharmacokinetics, pharmacodynamics, pharmacogenomics: Acetaminophen hepatic metabolism (glucuronidation/sulfation, toxic NAPQI via CYP2E1); nonsteroidals renal clearance; pharmacogenomics cytochrome P450 2C9 variants affect ibuprofen metabolism.

iii. Interactions/indications/contraindications: Nonsteroidals with anticoagulants increase bleeding (via platelet inhibition); indicated for inflammatory pain. Acetaminophen with alcohol increases hepatotoxicity.

iv. Specific drugs: Aspirin/ibuprofen/naproxen/diclofenac (non-selective); celecoxib (cyclooxygenase-2 selective, reduced gastrointestinal risk); acetaminophen; phenazone (pyrazolone derivative, anti-inflammatory).

v. Adverse effects: Nonsteroidals gastrointestinal (ulcers)/renal (acute kidney injury)/cardiovascular (myocardial infarction risk with cyclooxygenase-2); acetaminophen hepatotoxicity (>4 g/day).

vi. Other: Topical nonsteroidals for localized effect.

c. Antidepressants and Anticonvulsants

i. Antidepressants: Mechanism enhances descending inhibition via norepinephrine/serotonin reuptake inhibition in spinal cord (serotonin-norepinephrine reuptake inhibitors like duloxetine increase monoamines in dorsal horn synapses); sodium channel blockade for tricyclics (amitriptyline stabilizes membranes, reduces ectopic firing). Pharmacokinetics hepatic; interactions monoamine oxidase inhibitors (hypertensive crisis); indications neuropathic; drugs tricyclics (amitriptyline), serotonin-norepinephrine reuptake inhibitors (duloxetine), selective serotonin reuptake inhibitors (limited efficacy); adverse effects anticholinergic/sedation/weight gain.

ii. Anticonvulsants: Mechanism sodium/calcium channel blockade reduces ectopic firing (gabapentin/pregabalin bind alpha-2-delta subunit of voltage-gated calcium channels, decreasing glutamate release); gamma-aminobutyric acid enhancement (topiramate multiple mechanisms including gamma-aminobutyric acid potentiation). Pharmacokinetics renal/hepatic; interactions enzyme inducers (carbamazepine auto-induces); indications neuropathic; drugs gabapentin/pregabalin/carbamazepine/lamotrigine/topiramate; adverse effects dizziness/sedation/cognitive impairment.

iii. Other: Combination therapy, e.g., gabapentin with opioids for synergy.

d. Other Analgesic Pharmacotherapy

i. Neuroleptics: Dopamine-2 blockade reduces dopamine hyperactivity in pain pathways; hepatic pharmacokinetics; QT prolongation interactions; adverse extrapyramidal symptoms.

ii. Antihistamines: Histamine-1 blockade reduces central histamine-mediated pain facilitation; sedation adverse effects.

iii. Central nervous system stimulants: Dopamine/norepinephrine enhancement modulates attention and pain gating; for comorbid attention deficit hyperactivity disorder.

iv. Corticosteroids: Anti-inflammatory via phospholipase A2 inhibition, reducing arachidonic acid/prostaglandins; osteoporosis adverse.

v. Muscle relaxants/antispasticity: Gamma-aminobutyric acid B agonism (baclofen inhibits monosynaptic reflexes spinally); central (cyclobenzaprine, serotonin antagonism); sedation.

vi. Ketamine/N-methyl-D-aspartate antagonists: N-methyl-D-aspartate blockade prevents wind-up and central sensitization by blocking calcium influx; dissociative effects via glutamate surge.

vii. Local anesthetics/membrane-stabilizing: Sodium channel blockade prevents action potential propagation; systemic toxicity (seizures/cardiac arrest).

viii. Sympatholytics: Alpha/beta blockade reduces sympathetic outflow and vasoconstriction in sympathetically maintained pain; hypotension.

ix. Benzodiazepines: Gamma-aminobutyric acid A enhancement hyperpolarizes neurons, reducing anxiety-amplified pain; dependence.

x. Botulinum toxin: Acetylcholine release blockade at neuromuscular junction, reducing muscle spasm; spread effects to adjacent muscles.

xi. Transient receptor potential vanilloid-1 agonists (capsaicin): Initial activation followed by desensitization/depletion of substance P from C-fibers; burning sensation.

xii. Alpha-2 adrenergics (clonidine/tizanidine): Presynaptic alpha-2 agonism reduces norepinephrine release spinally, inhibiting transmission; sedation.

xiii. Other vasoactives (terazosin/verapamil): Alpha-1 blockade (vasodilation)/calcium channel blockade (smooth muscle relaxation).

xiv. Cannabinoids: Cannabinoid-1 (central analgesia via G-protein inhibition)/cannabinoid-2 (peripheral anti-inflammatory) agonism; psychiatric/cognitive effects.

xv. Ziconotide/calcium blockers: N-type voltage-gated calcium channel blockade in dorsal horn, reducing neurotransmitter release; intrathecal psychiatric effects (hallucinations).

xvi. Miscellaneous: E.g., calcitonin (inhibits osteoclasts for bone pain); St. John's wort interactions include induction of cytochrome P450 3A4 and P-glycoprotein, reducing levels of analgesics like fentanyl (CYP3A4 substrate), antidepressants (serotonin syndrome with selective serotonin reuptake inhibitors via serotonin excess), and anticonvulsants (reduced carbamazepine levels).

4. Treatment of Pain: Procedural

a. General Considerations

i. Preprocedural factors: Evaluate health status (coagulation/comorbidities).

ii. Indications/appropriateness: Evidence-based (e.g., epidural steroid injection for radiculopathy).

iii. Fluoroscopic imaging/radiation safety: As low as reasonably achievable; protective gear.

iv. Ultrasound guidance: Basics (probe/transducer); techniques (in/out-plane); risks (infection).

v. Drug selection: Steroids (depo-medrol); contrast (iohexol).

vi. Infection risk: Antibiotic prophylaxis if immunocompromised; sterile technique.

vii. Other: Informed consent/complication management.

b. Nonsurgical Stimulation-Produced Analgesia

i. Peripheral stimulation techniques: Transcutaneous electrical nerve stimulation (high-frequency for gate control), acupressure, acupuncture, electroacupuncture, vibration.

ii. Postulated mechanisms: Gate theory (large-fiber activation inhibits small-fiber pain in dorsal horn); endogenous opioid release (low-frequency); segmental inhibition for conventional transcutaneous electrical nerve stimulation, extrasegmental for acupuncture-like; central descending modulation via periaqueductal gray.

iii. Clinical applications and efficacy: Chronic musculoskeletal; evidence moderate.

iv. Other: Pulsed electromagnetic fields.

c. Injections, Nerve Blocks, and Lesioning

i. Nerve blocks/neurolytic: Diagnostic/therapeutic; indications (cancer/neuropathic); risks (infection/bleed); anatomy/pharmacology (alcohol/phenol for destruction via protein denaturation and axonolysis). Cranial (trigeminal branches for facial pain); peripheral (genicular for knee osteoarthritis); regional plane (transversus abdominis for abdominal wall; erector spinae for thoracic/back; serratus for chest wall; pectoralis for breast/chest). Musculoskeletal/intra-articular (e.g., steroid for inflammation reduction). Neuraxial (spinal/epidural interlaminar/transforaminal/caudal/nerve root for radiculopathy). Facet/zygapophyseal (medial branch blocks for diagnostic, steroid for inflammation). Radiofrequency ablation (cervical/thoracic/lumbar/sacral via thermal coagulation at 80°C for denervation). Sympathetic ganglion and plexus blocks: Stellate (targets head/neck/upper extremities for complex regional pain syndrome/ischemic pain); celiac (upper abdominal viscera like stomach/liver/pancreas/spleen for cancer pain); lumbar (lower extremities for vascular insufficiency/complex regional pain syndrome); hypogastric (pelvic organs like bladder/uterus/prostate for pelvic pain); impar (perineum/coccyx/rectum for coccydynia).

ii. Side effects/risks: Recognition/treatment (local anesthetic toxicity with seizures/cardiac arrest); complications (pneumothorax for thoracic); anticoagulation management per American Society of Regional Anesthesia guidelines (hold warfarin/aspirin based on risk).

iii. Vertebral augmentation (kyphoplasty/vertebroplasty): Indications compression fractures; benefits pain relief via stabilization; risks cement embolism/pulmonary.

iv. Other: Cryoablation (cold-induced necrosis at -20°C to -100°C).

d. Neuromodulation (Implanted Devices): Indications, Benefits, Risks, Associated Complications

i. Implanted stimulation: Spinal cord stimulation (paresthesia/burst/high-frequency via gate control and dorsal horn inhibition); dorsal root ganglion stimulation (T-junction filtering reduces ectopic signals, modulates somata); peripheral nerve stimulation.

ii. Spinal drug delivery: Intrathecal pumps/infusions (morphine starting 0.1-0.5 mg/day, titrate to 1-10 mg/day; ziconotide starting 0.5-2.4 mcg/day, max 19.2 mcg/day due to narrow window; baclofen 50-1000 mcg/day for spasticity); epidural implants. Benefits include targeted delivery with lower systemic doses; risks infection, granuloma, tolerance.

iii. Other: Deep brain stimulation for cluster headaches.

e. Neuroablative Pain Management

i. Ablative procedures: Cordotomy/dorsal root entry zone/neurolytic for cancer; indications refractory; risks paralysis; brain/stem/spinal/peripheral; cervical/thoracic/lumbar.

ii. Intrathecal/visceral/peripheral neurolysis: Techniques (radiofrequency/chemical); drugs (phenol/alcohol).

iii. Other: Gamma knife radiosurgery.

f. Regenerative Pain Medicine

i. Environmental products: Hyaluronic acid/amniotic fluid/platelet-rich plasma; risks infection; benefits regeneration via growth factors/anti-inflammatory.

ii. Cellular products: Lipoaspirate/bone marrow aspirate/umbilical cord/stem cells; risks tumorigenic; benefits musculoskeletal repair.

iii. Clinical uses/evidence: Osteoarthritis/joints; limited randomized controlled trials.

iv. Other: Exosomes.

5. Treatment of Pain: Psychological, Physical, and Integrative Therapies

a. Cognitive-Behavioral and Behavioral Interventions

i. Cognitive and behavioral strategies application: To syndromes like temporomandibular joint pain/neck/back/fibromyalgia/arthritis/burn/postoperative.

ii. Integration: Cognitive-behavioral with drugs for economic benefits.

iii. Stages of behavioral change: Precontemplation to maintenance; affects readiness for self-management.

iv. Common process factors: Rapport/hope/therapeutic alliance/communication/support/suggestion.

v. Solution-focused brief therapy/mindfulness-based/family/hypnosis/guided imagery/biofeedback/progressive muscle relaxation. Mechanisms: Alter maladaptive cognitions (reduce catastrophizing), enhance coping via neuroplasticity (decreased amygdala fear activation), enhance self-efficacy.

vi. Other: Operant conditioning.

b. Mental Health Treatment

i. Role of biofeedback/operant therapy/mindfulness/cognitive-behavioral therapy/hypnosis/relaxation/motivational enhancement.

ii. Psychiatric/psychological factors impacting adherence/alliance: E.g., psychological factors affecting medical conditions.

iii. Pharmacotherapy for comorbidities: Antidepressants/mood stabilizers/anxiolytics/antipsychotics.

iv. Psychotherapy for depression: Cognitive-behavioral/marital/family/interpretive/group.

v. Differential diagnosis of anxiety disorders augmenting pain.

vi. Anger in chronic pain: Increases perceived pain.

vii. Somatic complaints: Conversion (functional neurological symptom)/somatic symptom/illness anxiety disorders.

viii. Role of education/fear avoidance/self-esteem/efficacy/control/sick role/illness behavior/individual differences in affective/cognitive/behavioral responses.

ix. Coping styles: Definition/effect on outcomes/maintenance/catastrophizing.

x. Cultural/environmental factors: Effect on outcomes/maintenance.

xi. Family role: Interviewing/training/evaluating relatives.

xii. Patient beliefs/expectations: Influence disability/coping.

xiii. Sleep disorders in chronic pain: Diagnosis/evaluation.

xiv. Work history/education in chronic pain evaluation.

xv. Other: Trauma-informed care.

c. Physical Medicine and Rehabilitation Modalities and Treatment

i. Role of physiotherapy: Pacing/graded activity/passive/active therapy/manual therapy/exercise prescription.

ii. Temperature modalities: Heat/cold/ultrasound.

iii. Physical modalities: Manipulation/mobilization/massage/traction.

iv. Casting/splinting.

v. Exercise therapy.

vi. Other: Orthotics.

d. Work Rehabilitation and Management of Return to Work

i. Early intervention/return to work: Reduces absence.

ii. Psychosocial factors as main disability determinants/predictors of prolonged absence.

iii. Obstacles to recovery: Fear of reinjury/low expectations/mood/anxiety/withdrawal/passive treatments/negative attitude to activity/self-management.

iv. Successful rehabilitation components: General exercise/cognitive therapy/vocational.

v. Multidisciplinary approaches: Active exercise/addressing beliefs/enhancing coping/promoting self-management.

vi. Functional capacity evaluation: Definition/usefulness/limitations (subjective).

vii. Other: Ergonomics.

e. Complementary and Integrative Therapies (CAM)

i. Range: Alternative systems (traditional Chinese medicine/homeopathy/mind-body/energy); biologically based (herbs/foods/vitamins); manipulative (osteopathy).

ii. Acupuncture/acupressure/dry needling: Principles (meridians/qi); techniques/indications; clinical outcomes/evidence moderate; mechanisms include segmental inhibition and descending modulation.

iii. Prevalence/patient reasons: 30% use for autonomy.

iv. Evidence-based: Acupuncture moderate for pain.

v. Implications/costs/side effects: Drug interactions (e.g., St. John's wort with analgesics/antidepressants/anticonvulsants as detailed in pharmacotherapy).

vi. Other: Yoga/tai chi.